Lysine-Specific Demethylase 1 (LSD1) epigenetically controls osteoblast differentiation

Epigenetic mechanisms regulate osteogenic lineage differentiation of mesenchymal stromal cells. Histone methylation is controlled by multiple lysine demethylases and is an important step in controlling local chromatin structure and gene expression. Here, we show that the lysine-specific histone demethylase Kdm1A/Lsd1 is abundantly expressed in osteoblasts and that its suppression impairs osteoblast differentiation and bone nodule formation in vitro. Although Lsd1 knockdown did not affect global H3K4 methylation levels, genome-wide ChIP-Seq analysis revealed high levels of Lsd1 at gene promoters and its binding was associated with di- and tri-methylation of histone 3 at lysine 4 (H3K4me2 and H3K4me3). Lsd1 binding sites in osteoblastic cells were enriched for the Runx2 consensus motif suggesting a functional link between the two proteins. Importantly, inhibition of Lsd1 activity decreased osteoblast activity in vivo. In support, mesenchymal-targeted knockdown of Lsd1 led to decreased osteoblast activity and disrupted primary spongiosa ossification and reorganization in vivo. Together, our studies demonstrate that Lsd1 occupies Runx2-binding cites at H3K4me2 and H3K4me3 and its activity is required for proper bone formation.</p

Abstract 248: Structural Analysis of Aspiration Catheters and Procedural Outcomes: An Analysis of the SVIN Registry

Introduction Rapid expansion of mechanical thrombectomy and swift manufacturing development has translated into significant evolution of large bore catheter technology. The objective of this study was to evaluate the association among diverse structural components of large bore aspiration catheters on procedural performance. Methods Retrospective analysis of a prospectively maintained mechanical thrombectomy consortium (SVIN Registry) treated with stand‐alone contact aspiration for the first pass in the MCA M1 or intracranial ICA occlusions from 2012‐2021. Catheters were stratified based on construction materials, tip technology, catheter sizing, and catheter lining. Factors associated with first pass effect (FPE ‐ first‐pass eTICI2c‐3 reperfusion) as well as speed of clot engagement were analyzed. Results We identified 983 patients with proximal occlusion and aspiration as the first pass technique. FPE was observed in 34% and associated with age (OR:1.016;95%CI:1.006‐1.027), cardioembolic stroke etiology (OR:1.685;95%CI:1.77 ‐2.41), MCA M1(OR:2.737;95%CI:1.091 ‐1.867), non‐general anesthesia (OR:0.546;95%CI:0.389 ‐0.767), as well as with 0.070” (OR:2.038;95%CI:1.099 ‐3.779) and 0.088” (OR:3.899;95%CI:1.582 ‐9.606) distal catheter inner diameter in the adjusted analysis. Median time from arterial access to clot contact was 17 minutes with faster times observed in younger patients (OR:0.986;95%CI:0.975 ‐0.996) as well as with the use of aspiration catheters with shorter length of distal outer hydrophilic coating (18‐30cm) on multivariable regression (OR:0.303; 95%CI:0.113‐0.816). Conclusion Larger aspiration catheter distal inner diameter was associated with higher rates of FPE. Aspiration catheters with reduced distal tip hydrophilic coating were associated with faster arterial access to clot contact time